The objectives of this study are to ascertain biological, physiological and clinical mechanisms of male reproductive disorders and to provide rational strategies of treatment for men with reproductive disease. This project represents a continuum of research begun in 1970 and includes studies of 1) the hormonal regulation of spermatogenesis in gondadotropin deficient men, 2) biology of sperm function, 3) adverse effects of cancer therapy on gonadal function, 4) evaluation of treatment of men with reproductive disorders and 5) the role of sex steroids in regulation of gonadotropin secretion. Major findings from studies performed this year have shown 1) pulsatile GnRH in gonadotropin deficient men enhances testicular growth above that achieved with gonadotropins but sperm production is not facilitated, 2) subjects with Kallmann's syndrome show evidences for subtle neurological deficits which may serve as markers for the genetic disorder, 3) semen from infertile men show subpopulations of sperm on the basis of linear velocity characteristics, which may be important as a marker of infertility, 4) biodegradable testosterone microspheres appear to provide long-term androgen replacement in hypogonadal men, which offers a potentially practical therapy for men who desire infrequent parenteral injections.